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非整倍体与 TP53 表达相关,但与散发性结直肠癌中的 BRCA1 或 TERT 表达无关。

Aneuploidy is associated with TP53 expression but not with BRCA1 or TERT expression in sporadic colorectal cancer.

机构信息

The Pathology Clinic, Oslo University Hospital - Rikshospitalet, 0027 Oslo, Norway.

出版信息

Anticancer Res. 2009 Nov;29(11):4381-7.

Abstract

BACKGROUND

Defective expression of genes involved in mitotic chromosome segregation (e.g. AURKA, BUB1B), DNA damage response (e.g. TP53, BRCA1), and telomere function (e.g. TERT) may play a role in the development of tumor aneuploidy.

MATERIALS AND METHODS

The levels of TP53, BRCA1 and TERT were assessed in 55 sporadic colorectal tumors and 37 normal mucosas using tissue microarrays and immunohistochemical detection, and their associations with DNA aneuploidy, levels of mitotic spindle proteins AURKA, AURKB, MAD2L1 and BUB1B and clinicopathological parameters were investigated.

RESULTS

DNA aneuploidy was associated only with TP53 alterations. BRCA1 expression in tumors was significantly correlated with individual mitotic spindle protein expressions, and TERT and MAD2L1 expressions were moderately correlated in the tumor group, suggesting a putative role for TERT in MAD2L1 regulation.

CONCLUSION

Loss of TP53 function appears to be involved in the development of aneuploidy, but not in the deregulation of mitotic spindle protein function.

摘要

背景

有丝分裂染色体分离(如 AURKA、BUB1B)、DNA 损伤反应(如 TP53、BRCA1)和端粒功能(如 TERT)相关基因表达缺陷可能在肿瘤非整倍体的发生中起作用。

材料与方法

采用组织微阵列和免疫组织化学检测方法,评估了 55 例散发性结直肠肿瘤和 37 例正常黏膜中 TP53、BRCA1 和 TERT 的水平,并研究了它们与 DNA 非整倍体、有丝分裂纺锤体蛋白 AURKA、AURKB、MAD2L1 和 BUB1B 的水平以及临床病理参数的关系。

结果

DNA 非整倍体仅与 TP53 改变相关。肿瘤中 BRCA1 的表达与单个有丝分裂纺锤体蛋白的表达显著相关,而在肿瘤组中 TERT 和 MAD2L1 的表达呈中度相关,提示 TERT 可能参与 MAD2L1 的调节。

结论

TP53 功能丧失似乎参与了非整倍体的发生,但不参与有丝分裂纺锤体蛋白功能的失调。

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